CUDC-427 (GDC-0917)

Animal experiment:

Briefly, 10 million MDA-MB-231-X1.1 breast adenocarcinoma cells resuspended in Hank’s balanced salt solution and Matrigel (1:1, v/v) are implanted subcutaneously into the upper right flank of female SCID.bg mice. MDA-MB-231-X1.1 cells are MDA-MB-231 cells that are selected for improved in vivo growth rates. When tumor volumes reach approximately 100-300 mm3, mice are assigned to treatment groups to get a similar mean tumor size for each treatment group. Treatment groups (n=5 per group) are administered once daily oral doses of vehicle (15% hydroxypropyl-β-cyclodextrin, 20 mM succinic acid in water), 0.08, 0.17, 0.34, 0.68, 1.36, 2.72, 5.43, 10.87, or 16.30 mg/kg of GDC-0917 for 21 days. Tumor volumes are measured in two dimensions (length and width) using Ultra Cal IV calipers. Tumor sizes and body weights are recorded twice weekly, and the mice are regularly observed over the course of the study. Mice are euthanized if their tumor volume exceeds 2000 mm3 or if their body weight drops by more than 20% of the starting weight.

References:

[1]. Wong H, et al. Learning and confirming with preclinical studies: modeling and simulation in the discovery of GDC-0917, an inhibitor of apoptosis proteins antagonist. Drug Metab Dispos. 2013 Dec;41(12):2104-13.